Kluijver Louisa G, Wagenmakers Margreet A E M, Wilson J H Paul, Langendonk Janneke G
Porphyria Center Rotterdam, Center for Lysosomal and Metabolic Disease, Department of Internal Medicine, Erasmus MC, Erasmus University Medical Center, 3000 WB, Rotterdam, The Netherlands.
J Clin Endocrinol Metab. 2025 May 19;110(6):1633-1646. doi: 10.1210/clinem/dgae729.
Erythropoietic protoporphyria (EPP) is a rare inherited metabolic disease, causing lifelong painful phototoxic reactions, minimal sunlight exposure, and vitamin D deficiency. Previous studies reported a high osteoporosis prevalence in EPP patients.
To identify those at risk for low bone mineral density (BMD) and assess which factors, including treatment with cholecalciferol and afamelanotide, improve BMD in EPP.
A longitudinal ambispective single-center cohort study. Data from patient files and two-time questionnaires from adult patients with EPP who underwent at least one dual-energy x-ray absorptiometry (DXA) scan between 2012 and 2023 were used.
BMD is low in EPP patients, with 82.7% of the 139 patients having a Z-score below 0 SD at baseline. Low BMD classified as osteopenia was found in 39.5%, and osteoporosis in 15.3%. There were 50 osteoporosis-related fractures in 34.2% of patients. Aging (odds ratio [OR] 1.08; CI, 1.03-1.12), persistent vitamin D deficiency (OR 1.11; 95% CI, 1.00-1.23) and a low body mass index (OR 0.91; 95% CI, 0.82-0.99) increased the odds of low BMD. Patients with a vitamin D deficiency (OR 5.51; 95% CI, 1.69-17.92) and no cholecalciferol at baseline (OR 0.22; 95% CI, 0.04-1.34) had the highest odds of improving their BMD. Afamelanotide did not improve BMD.
25-hydroxyvitamin D (25(OH)D) status plays a crucial role in both preventing low BMD and improving BMD. EPP is a natural model for lack of sunlight exposure and vitamin D deficiency, underlining the importance of lifelong adequate vitamin D status for bone health in the general population.
红细胞生成性原卟啉病（EPP）是一种罕见的遗传性代谢疾病，会导致终身疼痛性光毒性反应、极少的阳光暴露以及维生素D缺乏。既往研究报道EPP患者骨质疏松患病率较高。
确定骨密度（BMD）低风险人群，并评估包括胆钙化醇和阿法美拉肽治疗在内的哪些因素可改善EPP患者的骨密度。
一项纵向双前瞻性单中心队列研究。使用了2012年至2023年间接受至少一次双能X线吸收测定（DXA）扫描的成年EPP患者的病历数据和两次问卷调查数据。
EPP患者骨密度较低，139例患者中有82.7%在基线时Z值低于0标准差。39.5%的患者骨密度低被分类为骨质减少，15.3%的患者为骨质疏松。34.2%的患者发生了50例与骨质疏松相关的骨折。年龄增长（比值比[OR]1.08；可信区间[CI]，1.03 - 1.12）、持续性维生素D缺乏（OR 1.11；95%CI，1.00 - 1.23）和低体重指数（OR 0.91；95%CI，0.82 - 0.99）增加了骨密度低的几率。维生素D缺乏的患者（OR 5.51；95%CI，1.69 - 17.92）和基线时未使用胆钙化醇的患者（OR 0.22；95%CI，0.04 - 1.34）骨密度改善几率最高。阿法美拉肽未改善骨密度。
25 - 羟基维生素D（25(OH)D）状态在预防骨密度低和改善骨密度方面都起着关键作用。EPP是阳光暴露不足和维生素D缺乏的天然模型，强调了终身充足的维生素D状态对普通人群骨骼健康的重要性。
